Proliferation Of Retinal Cells Research Articles

BMSC-derived exosomes attenuate persistent corneal epithelial injury by affecting retinal neural-like cells

Persistent corneal epithelial defect (PED) is a challenge to human which is difficultly cured, normally requiring long-term follow-up. Herein, this study explored the potential role of bone marrow mesenchymal stem cell-derived exosomes (BMSC-exos) in persistent corneal epithelial injury and the underlying mechanism. After characterization of BMSC-exos, RGC-5 cell viability was determined and surface markers of BMSCs were analyzed. Additionally, RT-qPCR and Western blot measured miR-150-5p, Brn3, Islet-1, and PCNA expression. Dual luciferase assays were conducted to evaluate the targeting relationship between long non-coding Ribonucleic Acid (lncRNA) MIAT and miR-150-5p. Presented in ellipsoidal or cup shape, BMSC-exos were positive to BMSC-specific markers CD29 and CD90, and cell surface markers CD9 and CD63 were detected on exosomes. Importantly, treatment with BMSC-exos significantly promoted proliferation of retinal ganglion cells (RGCs) and hindered cell differentiation. Interestingly, down-regulating lncRNA MIAT exerted the same effect as BMSC-exos, increasing cell viability and decreasing the expression of differentiation-related proteins Brn3 and ISL1. Bioinformatics software predicted miR-150-5P as target of lncRNA MIAT, and the relative luciferase activity of miR-150-5P+MIAT-WT co-transfection group was lower. Conclusively, BMSC-exos can improve PED by targeting and regulating miR-150-5p expression through lncRNA MIAT, which can up-regulate PCNA in RGC-5 cells and down-regulate Brn3 and ISL1.

Mutant kri1l causes abnormal retinal development via cell cycle arrest and apoptosis induction

Damage to the ribosome or an imbalance in protein biosynthesis can lead to some human diseases, such as diabetic retinopathy (DR) and other eye diseases. Here, we reported that the kri1l gene was responsible for retinal development. The kri1l gene encodes an essential component of the rRNA small subunit processome. The retinal structure was disrupted in kri1l mutants, which resulted in small eyes. The boundaries of each layer of cells in the retina were blurred, and each layer of cells was narrowed and decreased. The photoreceptor cells and Müller glia cells almost disappeared in kri1l mutants. The lack of photoreceptor cells caused a fear of light response. The development of the retina started without abnormalities, and the abnormalities began two days after fertilization. In the kri1l mutant, retinal cell differentiation was defective, resulting in the disappearance of cone cells and Müller cells. The proliferation of retinal cells was increased, while apoptosis was also enhanced in kri1l mutants. γ-H2AX upregulation indicated the accumulation of DNA damage, which resulted in cell cycle arrest and apoptosis. The kri1l mutation reduced the expression of some opsin genes and key retinal genes, which are also essential for retinal development.

The Influence of Electrical Stimulation on the Proliferation and Differentiation of Retinal Progenitor Cells

The Influence of Electrical Stimulation on the Proliferation and Differentiation of Retinal Progenitor Cells

Platelet-activating factor receptor (PAFR) regulates neuronal maturation and synaptic transmission during postnatal retinal development.

Platelet-activating factor (PAF), PAF receptor (PAFR), and PAF- synthesis/degradation systems are involved in essential CNS processes such as neuroblast proliferation, differentiation, migration, and synaptic modulation. The retina is an important central nervous system (CNS) tissue for visual information processing. During retinal development, the balance between Retinal Progenitor Cell (RPC) proliferation and differentiation is crucial for proper cell determination and retinogenesis. Despite its importance in retinal development, the effects of PAFR deletion on RPC dynamics are still unknown. We compared PAFR knockout mice (PAFR-/-) retinal postnatal development proliferation and differentiation aspects with control animals. Electrophysiological responses were analyzed by electroretinography (ERG). In this study, we demonstrate that PAFR-/- mice increased proliferation during postnatal retinogenesis and altered the expression of specific differentiation markers. The retinas of postnatal PAFR-/- animals decreased neuronal differentiation and synaptic transmission markers, leading to differential responses to light stimuli measured by ERG. Our findings suggest that PAFR signaling plays a critical role in regulating postnatal RPC cell differentiation dynamics during retinal development, cell organization, and neuronal circuitry formation.

Hyaluronan-Sphingosine Polymersomes for Treatment of Ocular Neovascularization: Synthesis and Evaluation.

Ocular neovascularization is a hallmark of several sight-threatening diseases, including diabetic retinopathy and age-related macular degeneration. Currently, available treatments are limited and often associated with side effects. Therefore, a novel approach to ocular neovascularization treatment through utilization of polymersomes from self-assembled sphingosine-grafted hyaluronic acid (HA-Sph) amphiphilic polymers is presented. The polymersomes are generated in spherical morphologies and sizes between 97.95- 161.9nm with homogenous size distributions. Experiments reveal that HA-Sph polymersomes, with concentrations ≥150µg mL-1 , significantly inhibit the proliferation of human umbilical vein endothelial cells (HUVECs), while concurrently promoting the proliferation of retinal pigment epithelial cells. The polymersomes demonstrate gradual disintegration in vitro, leading to sustained release of sphingosine, which prolongs the inhibition of HUVEC proliferation (from 87.5% at 24h to 35.2% viability at 96h). The efficacy of polymersomes in inhibiting angiogenesis is confirmed through tube formation assay, revealing a substantial reduction in tube length compared to the control group. The findings also validate the ocular penetration capability of polymersomes through ex vivo whole porcine eye ocular penetration study, indicating their suitability for topical administration. Potentially, HA-Sph polymersomes can be harnessed to develop intricate drug delivery systems that protect the retina and effectively treat ocular diseases.

Hyaluronan-CD44 Interaction Regulates Mouse Retinal Progenitor Cells Migration, Proliferation and Neuronal Differentiation

Cell-based therapies have shown great potential because of their abilities to replace dying retinal neuron cells and preserve vision. The migration, proliferation and differentiation of retinal progenitor cells(RPCs) plays a vital role in the integration of the RPCs into the retina when transplanted into the host. Our study aimed to explore the effects of Hyaluronan(HA)-CD44 interactions on the regulation of RPCs migration, proliferation and differentiation, and investigate the underlying regulatory mechanisms. We found that CD44 was expressed in RPCs, and the HA-CD44 interaction markedly improved RPCs adhesion and migration. The stimulation of microRNA-21(miR-21) expression by the HA-CD44 interaction was protein kinase C (PKC)/Nanog-dependent in RPCs. Treatment of RPCs with PKC- or Nanog-specific ASODN or miR-21 antagomir effectively blocked HA-mediated RPCs adhesion and migration. Moreover, Rho-Kinase(ROK)/ Grb2-associated binders(Gab-1) associated phosphatidylinositol 3-kinase(PI3K)/AKT signalling activation was required for HA-CD44 interaction mediated RPCs proliferation and neuronal differentiation. Our findings demonstrated new roles for the HA-CD44 interaction in regulating the migration, proliferation and neuronal differentiation of RPCs. HA-CD44 signalling could represent a novel approach to controlling RPC fates, and the findings may be instructive for the application of RPCs for future therapeutic applications.Graphical

석결명이 TGF-β1로 유도된 망막색소상피세포의 증식에 미치는 영향

석결명이 TGF-β1로 유도된 망막색소상피세포의 증식에 미치는 영향

Comparative study of Curcumin and Lucentis on retinal neovascularization

Introduction To investigate the effect of Curcumin on retinal neovascularization in mice with oxygen-induced lesions. Methods 7-day-old (P7) C57/BL6J mice were randomly divided into control group, OIR group, DMSO group, 100 mg/kg, 50 mg/kg and 25 mg/kg curcumin group and Lucentis group (15 mice per group). Mice in the experimental group were fed for 5 days in high oxygen partial pressure environment, and then in normal oxygen air environment for another 5 days. Corresponding interventions were given at 12-16 days of age (P12-16). At 17 days of age (P17), the eyeball was removed and the retina was paved with Isolectin GS-IB4 fluorescence staining. Real-time PCR was used to detect VEGF mRNA levels in tissues and cells. The protein expression level of VEGF was detected by Western blot. Results Immunofluorescence showed that curcumin injection could significantly reduce the formation of retinal neovascularization and astrocyte injury in OIR, and 100 mg/kg curcumin group had the best effect. Compared with the control group, mRNA and protein expression of VEGF in retina of mice in OIR and DMSO groups were significantly up-regulated (P<0.05); Compared with OIR group, curcumin group and Lucentis group were down-regulated (P<0.05). The protein expression and mRNA level of VEGF in HRCECs of curcumin group decreased with the increase of curcumin concentration, and the effect of curcumin group at 80μmol/L was similar to that of Lucentis group. In the HRCECs cultured with the same concentration of curcumin, the protein expression and mRNA level of VEGF decreased with the prolongation of drug intervention time. Conclusion Curcumin can down-regulate the expression of VEGF in retinal tissues and cells, thereby inhibiting retinal neovascularization and HRCECs cell proliferation.

Rod precursors in the adult retina of the Austrolebias charrua annual fish

Rod photoreceptors in the adult teleost retina are produced by rod precursors located in the outer nuclear layer (ONL). Annual fishes of the genus Austrolebias exhibit extensive adult retinal cell proliferation and neurogenesis, as well as surprising adaptive strategies to their extreme and changing environment, including adult retinal plasticity. Thus, here we identify and characterize rod precursors in the ONL of the Austrolebias charrua retina. For this aim we used classical histological techniques, transmission electron microscopy, detection of cell proliferation, and immunohistochemistry. Through these complementary approaches, we describe a cell population clearly distinguishable from photoreceptors in the ONL of the adult retina of A. charrua, which we propose corresponds to the rod precursor population. These cells exhibited particular morphological and ultrastructural characteristics, uptake of cell proliferation markers (BrdU+) and expression of stem cell markers (Sox2+). Determining the existence of the population of rod precursors is crucial to understand the sequence of events related to retinal plasticity and regeneration.

Loss of flrt2 gene leads to microphthalmia in zebrafish.

As a member of the fibronectin leucine-rich transmembrane (flrt) gene family, fibronectin leucine-rich transmembrane 2 (flrt2) is strongly expressed in a subset of sclerotome cells, and the resultant protein interacts with FGFR1 in the FGF signaling pathway during development. Studies on flrt2 have focused mainly on its roles in the brain, heart and chondrogenesis. However, reports on its expression and function in the zebrafish retina are lacking. Here, we detected the high expression of flrt2 in zebrafish retina using in situ hybridization technique and developed an flrt2-knockout (KO) zebrafish line using CRISPR/Cas9 genome editing. Quantitative real-time PCR was used to measure the expression levels of flrt2, which results in an approximately 60% mRNA reduction. The flrt2-KO zebrafish eyes' altered morphological, cellular, and molecular events were identified using BrdU labeling, TUNEL assay, immunofluorescent staining, fluorescent dye injection and RNA sequencing. Abnormal eye development, known as microphthalmia, was found in flrt2-KO larvae, and the retinal progenitor cells exhibited increased apoptosis, perhaps owing to the combined effects of crx, neurod4, atoh7, and pcdh8 downregulation and Casp3a and Caspbl upregulation. In contrast, the retinal neural development, as well as retinal progenitor cell differentiation and proliferation, were not affected by the flrt2 deletion. Thus, flrt2 appears to play important roles in retinal development and function, which may provide the basis for further investigations into the molecular mechanisms of retinal development and evolution.

TRANSCORNEAL INTRAVITREAL INJECTION TECHNIQUE FOR PEDIATRIC PATIENTS WITH APHAKIA AND POSTVITRECTOMIZED EYES.

BACKGROUND Although modern minimally invasive vitreoretinal surgery has improved visual outcomes, post-operative proliferative vitreoretinopathy (PVR) and hypotony remain a cause of poor visual results1,2. The migration and proliferation of retinal pigment epithelial cells and the invading immune cells lead to the formation of adherent membranes3. To prevent worsening of PVR and suppress intraocular inflammation, intravitreal triamcinolone, or in some cases, anti-vascular endothelial growth factor (anti-VEGF) have been used4,5. In cases of chronic hypotony, intravitreal triamcinolone injection is also thought to have a role in treatment2.

The histone H3K36 demethylase Fbxl11 plays pivotal roles in the development of retinal late-born cell types.

Histone methylation plays a vital role in retinal development. However, the role of histone H3K36 methylation in retinal development is not clear. We examined the role of H3K36 methylation by loss-of-function analysis of H3K36me1/2 demethylases, Fbxl10, and Fbxl11. We analyzed the effect of knockout of these genes in the developing and mature retina on retinal development. Knockout of Fbxl10 specifically in the developing retina did not result in gross developmental abnormalities. Although adult rod photoreceptor-specific knockout of Fbxl11 in mature retinas did not result in morphological abnormalities, Fbxl11 knockout in developing retinas increased apoptosis, suppressed the proliferation of retinal progenitor cells, and resulted in microphthalmia. Morphological analysis revealed perturbed differentiation of rod photoreceptor and bipolar cells. RNA-seq of retinas at P7 showed markedly decreased expression of genes characterizing rod photoreceptor and bipolar cells in Fbxl11-knockout retinas. In addition, perturbation of alternative splicing increased intron retention in Fbxl11-knockout retinas. Genome-wide evaluation of the H3K36 methylation status revealed that Fbxl11 knockout altered the distribution of H3K36me2/3 in genes important for rod photoreceptor development. Taken together, we show that Fbxl11 plays pivotal roles in the development of retinal late-born cell types and may contribute to tight control of H3K36 methylation during retinal development.

Intravitreal Short-Hairpin RNA Attenuated Adeno-Associated Virus-Induced Knockdown of Amphiregulin and Axial Elongation in Experimental Myopia.

Epidermal growth factor (EGF) and its family members have been reported to be involved in myopic axial elongation. We examined whether short hairpin RNA attenuated adeno-associated virus (shRNA-AAV)-induced knockdown of amphiregulin, an EGF family member, has an influence on axial elongation. Three-week-old pigmented guinea pigs underwent lens-induced myopization (LIM) without additional intervention (LIM group; n = 10 animals) or additionally received into their right eyes at baseline an intravitreal injection of scramble shRNA-AAV (5 × 1010 vector genome [vg]) (LIM + Scr-shRNA group; n = 10) or of amphiregulin (AR)-shRNA-AAV (5 × 1010 vg/5 µL) (LIM + AR-shRNA-AAV group; n = 10), or they received an injection of AR-shRNA-AAV at baseline and three weekly amphiregulin injections (20 ng/5 µL) (LIM + AR-shRNA-AAV + AR group; n = 10). The left eyes received equivalent intravitreal injections of phosphate-buffered saline. Four weeks after baseline, the animals were sacrificed. At study end, interocular axial length difference was higher (P < 0.001), choroid and retina were thicker (P < 0.05), and relative expression of amphiregulin and p-PI3K, p-p70S6K, and p-ERK1/2 was lower (P < 0.05) in the LIM + AR-shRNA-AAV group than in any other group. The other groups did not differ significantly when compared with each other. In the LIM + AR-shRNA-AAV group, the interocular axial length difference increased with longer study duration. TUNEL assay did not reveal significant differences among all groups in retinal apoptotic cell density. In vitro retinal pigment epithelium cell proliferation and migration were the lowest (P < 0.05) in the LIM + AR-shRNA-AAV group, followed by the LIM + AR-shRNA-AAV + AR group. shRNA-AAV-induced knockdown of amphiregulin expression, in association with suppression of epidermal growth factor receptor signaling, attenuated axial elongation in guinea pigs with LIM. The finding supports the notion of EGF playing a role in axial elongation.

Chromatin Remodeling Enzyme Snf2h Is Essential for Retinal Cell Proliferation and Photoreceptor Maintenance.

Chromatin remodeling complexes are required for many distinct nuclear processes such as transcription, DNA replication, and DNA repair. However, the contribution of these complexes to the development of complex tissues within an organism is poorly characterized. Imitation switch (ISWI) proteins are among the most evolutionarily conserved ATP-dependent chromatin remodeling factors and are represented by yeast Isw1/Isw2, and their vertebrate counterparts Snf2h (Smarca5) and Snf2l (Smarca1). In this study, we focused on the role of the Snf2h gene during the development of the mammalian retina. We show that Snf2h is expressed in both retinal progenitors and post-mitotic retinal cells. Using Snf2h conditional knockout mice (Snf2h cKO), we found that when Snf2h is deleted, the laminar structure of the adult retina is not retained, the overall thickness of the retina is significantly reduced compared with controls, and the outer nuclear layer (ONL) is completely missing. The depletion of Snf2h did not influence the ability of retinal progenitors to generate all the differentiated retinal cell types. Instead, the Snf2h function is critical for the proliferation of retinal progenitor cells. Cells lacking Snf2h have a defective S-phase, leading to the entire cell division process impairments. Although all retinal cell types appear to be specified in the absence of the Snf2h function, cell-cycle defects and concomitantly increased apoptosis in Snf2h cKO result in abnormal retina lamination, complete destruction of the photoreceptor layer, and consequently, a physiologically non-functional retina.

Gene Therapy Activates Retinal Pigment Epithelium Cell Proliferation for Age-related Macular Degeneration in a Mouse Model

Age-related macular degeneration (AMD) is a degenerative retinal disease. The degeneration or death of retinal pigment epithelium (RPE) cells is implicated in the pathogenesis of AMD. This study aimed to activate the proliferation of RPE cells in vivo by using an adeno-associated virus (AAV) vector encoding β-catenin to treat AMD in a mouse model. Mice were intravitreally injected with AAV2/8-Y733F-VMD2-β-catenin for 2 or 4 weeks, and β-catenin expression was measured using immunofluorescence staining, real-time quantitative reverse transcription polymerase chain reaction (PCR), and Western blotting. The function of β-catenin was determined using retinal flat mounts and laser-induced damage models. Finally, the safety of AAV2/8-Y733F-VMD2-β-catenin was evaluated by multiple intravitreal injections. AAV2/8-Y733F-VMD2-β-catenin induced the expression of β-catenin in RPE cells. It activated the proliferation of RPE cells and increased cyclin D1 expression. It was beneficial to the recovery of laser-induced damage by activating the proliferation of RPE cells. Furthermore, it could induce apoptosis of RPE cells by increasing the expression of Trp53, Bax and caspase3 while decreasing the expression of Bcl-2. AAV2/8-Y733F-VMD2-β-catenin increased β-catenin expression in RPE cells, activated RPE cell proliferation, and helped mice heal from laser-induced eye injury. Furthermore, it could induce the apoptosis of RPE cells. Therefore, it may be a safe approach for AMD treatment.

Urine-derived mesenchymal stem cells-derived exosomes enhances survival and proliferation of aging retinal ganglion cells

ObjectivesThis study was designed to investigate to test the effect of exosomes from urine-derived mesenchymal stem cells (USCs) on the survival and viability of aging retinal ganglion cells (RGCs), and explored the preliminary related mechanisms.MethodsPrimary USCs were cultured and identified by immunofluorescence staining. Aging RGCs models were established by D-galactose treatment and identified by β-Galactosidase staining. After treatment with USCs conditioned medium (with USCs removal), flow cytometry was performed to examine the apoptosis and cell cycle of RGCs. Cell viability of RGCs was detected by Cell-counting Kit 8 (CCK8) assay. Moreover, gene sequencing and bioinformatics analysis were applied to analyze the genetic variation after medium treatment in RGCs along with the biological functions of differentially expressed genes (DEGs).ResultsThe number of apoptotic aging RGCs was significantly reduced in USCs medium-treated RGCs. Besides, USCs-derived exosomes exert significant promotion on the cell viability and proliferation of aging RGCs. Further, sequencing data analyzed and identified DEGs expressed in aging RGCs and aging RGCs treated with USCs conditioned medium. The sequencing outcomes demonstrated 117 upregulated genes and 186 downregulated genes in normal RGCs group vs aging RGCs group, 137 upregulated ones and 517 downregulated ones in aging RGCs group vs aging RGCs + USCs medium group. These DEGs involves in numerous positive molecular activities to promote the recovery of RGCs function.ConclusionsCollectively, the therapeutic potentials of USCs-derived exosomes include suppression on cell apoptosis, enhancement on cell viability and proliferation of aging RGCs. The underlying mechanism involves multiple genetic variation and changes of transduction signaling pathways.

V-ATPase Regulates Retinal Progenitor Cell Proliferation During Eye Regrowth in Xenopus.

Purpose: The induction of retinal progenitor cell (RPC) proliferation is a strategy that holds promise for alleviating retinal degeneration. However, the mechanisms that can stimulate RPC proliferation during repair remain unclear. Xenopus tailbud embryos successfully regrow functional eyes within 5 days after ablation, and this process requires increased RPC proliferation. This model facilitates identification of mechanisms that can drive in vivo reparative RPC proliferation. This study assesses the role of the essential H+ pump, V-ATPase, in promoting stem cell proliferation. Methods: Pharmacological and molecular loss of function studies were performed to determine the requirement for V-ATPase during embryonic eye regrowth. The resultant eye phenotypes were examined using histology and antibody markers. Misexpression of a yeast H+ pump was used to test whether the requirement for V-ATPase in regrowth is dependent on its H+ pump function. Results: V-ATPase inhibition blocked eye regrowth. Regrowth-incompetent eyes resulting from V-ATPase inhibition contained the normal complement of tissues but were much smaller. V-ATPase inhibition caused a significant reduction in reparative RPC proliferation but did not alter differentiation and patterning. Modulation of V-ATPase activity did not affect apoptosis, a process known to be required for eye regrowth. Finally, increasing H+ pump activity was sufficient to induce regrowth. Conclusions: V-ATPase is required for eye regrowth. These results reveal a key role for V-ATPase in activating regenerative RPC proliferation and expansion during successful eye regrowth.

MiR-124-3p regulates the proliferation and differentiation of retinal progenitor cells through SEPT10.

Retinal degenerative diseases such as glaucoma, retinitis pigmentosa, and age-related macular degeneration pose serious threats to human visual health due to lack of effective therapeutic approaches. In recent years, the transplantation of retinal progenitor cells (RPCs) has shown increasing promise in the treatment of these diseases; however, the application of RPC transplantation is limited by both their poor proliferation and their differentiation capabilities. Previous studies have shown that microRNAs (miRNA) act as essential mediators in the fate determination of stem/progenitor cells. In this study, we hypothesized that miR-124-3p plays a regulatory role in the fate of RPC determination by targeting Septin10 (SEPT10) in vitro. We observed that the overexpression of miR124-3p downregulates SEPT10 expression in RPCs, leading to reduced RPC proliferation and increased differentiation, specifically towards both neurons and ganglion cells. Conversely, antisense knockdown of miR-124-3p was shown to boost SEPT10 expression, enhance RPC proliferation, and attenuate differentiation. Moreover, overexpression of SEPT10 rescued miR-124-3p-caused proliferation deficiency while weakening the enhancement of miR-124-3p-induced-RPC differentiation. Results from this study show that miR-124-3p regulates RPC proliferation and differentiation by targeting SEPT10. Furthermore, our findings enable a more comprehensive understanding into the mechanisms of proliferation and differentiation of RPC fate determination. Ultimately, this study may be useful for helping researchers and clinicians to develop more promising and effective approaches to optimize the use of RPCs in treating retinal degeneration diseases.

Insulin-like growth factor-1 stimulates retinal cell proliferation via activation of multiple signaling pathways.

Insulin-like growth factor-1 (IGF-1) plays critical roles in the development of the central nervous system (CNS), including the retina, regulating cell proliferation, differentiation, and survival. Here, we investigated the role of IGF-1 on retinal cell proliferation using primary cultures from rat neural retina. Our data show that IGF-1 stimulates retinal cell proliferation and regulates the expression of neurotrophic factors, such as interleukin-4 and brain-derived neurotrophic factor. In addition, our results indicates that IGF-1-induced retinal cell proliferation requires activation of multiple signaling pathways, including phosphatidylinositol 3-kinase, protein kinase Src, phospholipase-C, protein kinase C delta, and mitogen-activated protein kinase pathways. We further show that activation of matrix metalloproteinases and epidermal growth factor receptor is also necessary for IGF-1 enhancing retinal cell proliferation. Overall, these results unveil potential mechanisms by which IGF-1 ensures retinal cell proliferation and support the notion that manipulation of IGF-1 signaling may be beneficial in CNS disorders associated with abnormal cell proliferation.

Maternal Toxoplasma gondii infection affects proliferation, differentiation and cell cycle regulation of retinal neural progenitor cells in mouse embryo.

Toxoplasmosis affects one third of the world population and has the protozoan Toxoplasma gondii as etiological agent. Congenital toxoplasmosis (CT) can cause severe damage to the fetus, including miscarriages, intracranial calcification, hydrocephalus and retinochoroiditis. Severity of CT depends on the gestational period in which infection occurs, and alterations at the cellular level during retinal development have been reported. In this study, we proposed a mouse CT model to investigate the impact of infection on retinal development. Pregnant females of pigmented C57BL/6 strain mice were infected intragastrically with two T. gondii cysts (ME49 strain) at embryonic day 10 (E10), and the offspring were analyzed at E18. Infected embryos had significantly smaller body sizes and weights than the PBS-treated controls, indicating that embryonic development was affected. In the retina, a significant increase in the number of Ki-67-positive cells (marker of proliferating cells) was found in the apical region of the NBL of infected mice compared to the control. Supporting this, cell cycle proteins Cyclin D3, Cdk6 and pChK2 were significantly altered in infected retinas. Interestingly, the immunohistochemical analysis showed a significant increase in the population of β-III-tubulin-positive cells, one of the earliest markers of neuronal differentiation. Our data suggests that CT affects cell cycle progression in retinal progenitor cells, possibly inducing the arrest of these cells at G2/M phase. Such alterations could influence the differentiation, anticipating/increasing neuronal maturation, and therefore leading to abnormal retinal formation. Our model mimics important events observed in ocular CT.